Neurological diseases in the central nervous system are mostly characterized by the failure of endogenous repair to restore tissue damage and salvage lost function. Currently, studies have shown that neural stem cell transplantation provides a good therapeutic effect on neurological diseases. For this reason, neural stem cell transplantation has been explored as a cell replacement therapy. Although transplanted cells can replace cells lost during or post central nervous system injury, many studies have shown that this mechanism is insufficient as most of these newly formed cells fail to integrate and eventually die. Although it was initially thought that neural stem cell could only replace lost cells, recent experiments have shown that transplanted neural stem cell can also play bystander roles such as neuroprotection and immune regulation, promote tissue repair by preventing tissue damage, interfere with pathogenic processes, or by rescuing endogenous nerve cells. However, compelling evidence has raised concerns about this bystander effect, which can be caused by several biologically active molecules (collectively known as the secretome) produced by neural stem cells. These results also raise the possibility of the neural stem cell secretome as a potential candidate for neural stem cell transplantation therapies based on the bystander effect. A better understanding of the molecules and mechanisms of this effect is of critical importance for neural stem cell-based therapies. This review aims to discuss the function and application of neural stem cell secretome in the treatment of neurodegenerative disorders.